Abstract: Pancreatic cancer, the most lethal human cancer, remains a major unsolved healthcare problem. Close to 90% of new pancreatic cancer patients are diagnosed at a late stage after metastasis and die because there are no or few symptoms in its early stages. It has been projected that pancreatic cancer will be the second most fatal cancer by 2030 in the United States. Despite such discouraging statistics, early detection and screening strategies are currently not available. The goal of this proposal is to develop a new invention for the detection of pancreatic cancer in its early stage for the best chances at effective treatment. With PI?s expertise in biotechnology, three integrated specific aims are proposed to develop a next-generation platform for non-invasive exosome-based liquid biopsies in pancreatic cancer and fully validate it with sets of controls and unprocessed whole blood for implementation in a clinical routine. Our central hypothesis is that the integration of the unprecedented sensitivity of nanoscale electronic materials and the specificity of tumor-specific peptides allows us to detect, quantify, and distinguish the pancreatic cancer-exosome markers at the single-molecule level by direct electronic signal readouts. Initially, we will synthesize tumor-specific iRGD peptides, decorate them on the bio-transistor developed by the PI, determine their detection sensitivity, and identify control parameters for their effective detection of the pancreatic cancer exosome. Next, we will focus on identification and classification of the pancreatic cancer-exosomes using the electronic detection signals. We will adopt advanced data analysis including a machine-learning algorithm to determine a unique electronic ?fingerprint? for each exosome type and implement the un-biased, automatic data analysis for distinguishing one type from another. Finally, we will develop a microfluidic-based multilevel filtration system for on-chip plasma and exosome separation from whole blood, and integrate it with bio-transistors to realize and deliver a prototype, portable pancreatic cancer diagnostic device. The outcome of the proposed research will substantially impact the diagnosis, treatment, and prognosis of pancreatic cancer patients, as well as provide new possibilities for point-of-care, home diagnostics for people who have had cancer, are suffering from cancer, and are in a high-risk group.